Synthesis and SAR Study of Novel Amidino 2-substituted Benzimidazoles as Potential Antibacterial Agents

Abstract

A series of novel 2-substituted benzimidazole derivatives were synthesized and their antibacterial activity was assessed against selected Gram-positive and Gram-negative bacteria. The specific moiety at the 2-position of the benzimidazole was extensively modified with several fused heterocyclic functional groups containing nitrogen and sulfur heteroatoms. In addition, the influence of different amidino groups at the position 5 of benzimidazole scaffold was evaluated. The values of clogP (a partition coefficient) and clogD7.5 (calculated distribution coefficient, pH 7.5) were determined and the lipophilic character of compounds has been found to be important parameter for the observed activity of the tested benzimidazole derivatives against Moraxella catarrhalis. The indolo 2-substituted benzimidazole 13a demonstrated solid activity against Staphylococcus aureus (MICs 16 µg/mL) and Moraxella catarralis (MICs 2 µg/mL) and represents promising lead molecule for further optimization.

Novel tetrahydropyrimidinyl-substituted benzimidazoles and benzothiazoles: synthesis, antibacterial activity, DNA interactions and ADME profiling

“…Moraxella catarrhalis is a human-restricted pathogen responsible for respiratory tract infections such as childhood otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD) in adults. 11–13 It is the third most common cause of OM after Haemophilus influenzae and Streptococcus pneumoniae , is responsible for up to 20% of the cases and is the second most common cause of COPD, making it one of the primary medical issues related to bacteria. 14 To date, most therapeutic guidelines recommend antibiotics for the treatment of OM cases.…”

Design, synthesis, biological evaluation and QSAR analysis of novel N-substituted benzimidazole derived carboxamides

“…Furthermore, the benzimidazole structural motif was identified in many biologically important molecules with an important role for the interaction with enzymes and different proteins 7 , 8 . The broad range of biological activities of benzimidazole derivatives includes primarily antitumor 9 , antiviral 10 , antimicrobial, 11 anti-inflammantory 12 , antifungal 13 , antiprotozoal 14 , antihypertensive 15 , antioxidative 16 , etc. activities.…”